Female Reproductive System Lab

Learning Objectives

  • Explain the regular progression of follicular development and atresia occurring in a cyclic fashion in the primary ovary.
  • Describe the structural changes that occur in the uterus over the course of the menstrual cycle and pregnancy.
  • Characterize the histological features of the oviduct, uterus, cervix, and vagina, with particular attention to the mucosal linings of these tissues.
  • Describe the cellular organization of the placenta, including the juxtaposition of the maternal and fetal circulations.
  • Recognize some key pathology related to the female reproductive system.

Pre-Lab Reading

Overview of the Female Reproductive System

The female reproductive system is composed of two gonads known as ovaries, two oviducts, the uterus, the vagina and external genitalia, and two mammary glands. Its development, maturation, and functioning is dependent upon a complex interplay of hormones from the hypothalamus, pituitary gland, adrenal glands, ovaries, and placenta.

The system has six primary functions:

  • To produce ova via oogenesis
  • To receive spermatozoa
  • To provide an environment for fertilization
  • To provide an environment for fetal development
  • To expel the developed fetus
  • To provide nutrition to the newborn

Ovary

The ovary is the female gonad and is composed of two regions with indistinct boundaries:

  • An outer cortex , which is occupied by the developing follicles and contains several hundred thousand ova.
  • An inner medulla , which contains prominent blood vessels, nerves, and scattered clusters of interstitial cells.

The ovarian epithelium is a single layer of squamous or low columnar cells that forms the external covering of the ovary. It does not correspond to the germinal epithelium of the male seminiferous tubules, which is the site of sperm production and development.

Ovarian Follicles

There are several developmental stages that precede the maturation and release of the ovum. All of these occur within the cortex of the ovary:

  • Oogonia are small, diploid germ cells that migrate to the ovarian cortex and multiply by mitosis. Some of these cells develop the potential to become mature female gametes and become primordial follicles. This occurs during the first few months of gestation.
  • Primordial follicles consist of a primary oocyte surrounded by a layer of squamous follicular cells . The oocytes in these follicles undergo arrest before the completion of the first stage of meiosis, and therefore have double the genetic material of the oogonia (4N). This arrest continues until a female reaches sexual maturity.
  • After puberty, a few primordial follicles develop into primary follicles with each ovarian cycle. Like its primordial follicle precursor, the early primary follicle is encapsulated by a single layer of cuboidal epithelial cells. With continued development, this lining becomes stratified epithelium composed of cuboidal granulosa cells surrounded by an outer layer of squamous theca cells . The primary oocyte grows and becomes encased in an acellular layer of proteoglycans and glycoproteins known as the zona pellucida . This layer separates the developing oocyte from the surrounding granulosa cells.
  • As the follicle continues to develop, the oocyte is displaced from its center by the accumulation of the liquor folliculi in the developing follicular antrum . The formation of the antrum represents the transition to a secondary follicle . A group of cells known as the cumulus oophorus develops between the oocyte and the zona granulosa . The zona granulosa produces estrogen, whereas the theca interna produces androstenedione that is converted to estrogen by the enzyme aromatase in the granulosa cells. The outer theca externa has no known function.
  • With continuing hormonal stimulation, the first meiotic division is completed and a Graafian follicle develops. In this process, the primary oocyte becomes a secondary oocyte (2N) and the first polar body is formed. In this follicle, the oocyte is surrounded by the zona pellucida and a group of cells known as the corona radiata , which is derived from the cumulus oophorus. The follicle has a large fluid-filled antrum and is enveloped by follicular cells comprising the zona granulosa, as well as internal and external theca cells.

Upon ovulation, the Graafian follicle bursts and the ovum , composed of the oocyte, zona pellucida, and corona radiata is expelled into the peritoneal cavity near the oviduct. The second meiotic division and formation of the second polar body does not occur until fertilization.

Several primordial follicles enter each ovarian cycle, but typically only one ovum is released. The remaining follicles degenerate and are called atretic follicles . These follicles exhibit a glassy membrane between the granulosa and theca cells as well as a corpus fibrosum , or fibrous tissue infiltration of the follicular space.

Corpus Luteum

After ovulation, the portion of the follicle remaining in the ovary collapses and fills with blood, and its component cells undergo changes to form the corpus luteum . Granulosa cells develop into granulosa lutein cells and theca cells develop into theca lutein cells, and the corpus luteum begins secreting primarily progesterone and to a lesser extent estrogen, both of which are necessary to maintain the uterine lining to prepare for implantation.

At this point, the fate of the corpus luteum is determined by hormonal input that itself is determined by whether or not fertilization and implantation take place.

  • If fertilization does not take place, luteinizing hormone from the anterior pituitary ceases and the corpus luteum becomes the corpus albicans , a fibrous tissue mass with macrophage infiltration.
  • If fertilization and implantation do take place, hCG from the placenta rescues the corpus luteum, which becomes the corpus luteum of pregnancy . It continues to produce estrogen and progesterone as the placenta prepares to take on this role.

Genital Tract

The female genital tract collects the ovum released from the Graafian follicle and serves as the site of its potential fertilization and development into a fetus. It is composed of several tissues that differ from one another structurally and functionally. Nevertheless, these tissues have the same basic organization consisting of an inner mucosal lining, a muscular layer, and an outer connective tissue layer:

  • The oviducts or fallopian tubes transport the ovum from the ovary to the uterus and serve as the site of fertilization. They have a muscular wall with a folded mucosa composed of a ciliated columnar epithelium. The epithelium contains ciliated cells that move the ovum along and non-ciliated secretory cells that nourish and protect it. The oviducts are divided into four parts: infundibulum , ampulla , isthmus , and pars interstitialis . A thick epithelium and thin muscle layer characterize the former two regions; the latter two regions have more muscle and a thinner epithelium.
  • The uterus is the site of implantation. Its structure changes considerably based upon the stage of the menstrual cycle. Uterine structure throughout the menstrual cycle is covered in detail in the next section.
  • The cervix is the junction between the uterus and vagina. It protects the uterus and upper genital tract from bacterial invasion. The external os of the cervix represents an important transitional area between mucous-secreting endocervical cells on the uterine side to a stratified squamous epithelium on the vaginal side. Underlying the epithelium is a great deal of collagenous tissue containing numerous leukocytes, which protect against bacterial infiltration.
  • The vagina is the site of entry for the spermatozoa and exit for the fetus. The stratified squamous epithelium is notable for its production of glycogen, which is broken down into lactic acid as a defense mechanism against pathogens. The lamina propria of the vagina contains many elastic fibers and few glands. While mucous secretion does not come from the vagina itself, the lamina propria contains a vascular network that produces a transudate that serves as an additional lubricant. The vagina has inner circular and outer longitudinal layers of smooth muscle, and an adventitia that merges with that of the bladder and rectum.

The Uterus

The uterus is composed of three important layers:

  • The mucosa of the uterus is known as the endometrium. It is a columnar epithelium that contains numerous tubular glands. Some of the epithelial cells are ciliated while the rest contain microvilli. It has two component sub-layers. The stratum functionalis , which changes over the course of the cycle, and the stratum basalis , which remains relatively constant. The endometrium is highly vascularized, with a blood supply consisting of straight arteries that form a plexus in the stratum basalis and spiral arteries that extend to the surface of the stratum functionalis.
  • The muscularis layer of the uterus is the myometrium . It is a thick smooth muscle layer that expands during pregnancy and serves to protect and expel the fetus. The middle layer of the myometrium, the stratum vasculare , contains many large blood vessels.
  • The serosal layer of the uterus is the perimetrium . It is composed primarily of connective tissue.

The Uterine Cycle

The uterine cycle is characterized histologically by the different changes that take place in the endometrium. It is divided into several phases:

  • The proliferative phase begins at the end of the menstrual flow and is maintained by the production of estrogen by the developing follicles. In this phase, the endometrium is densely populated by fibroblasts and the uterine glands are small (10 micron) invaginations. From the day 8 to 14, the uterine glands elongate as the entire endometrium doubles or triples in thickness. The final endometrial thickness may be as much as five millimeters. During the late stages of this phase, blood vessels from the stratum vasculare invade the endometrium.
  • The secretory (luteal) phase begins at ovulation and is governed by progesterone production from the corpus luteum. The glands become closely packed, coiled, and dilated (> 50 microns). The columnar epithelium discharges a carbohydrate-rich secretion that nourishes the ovum. Coiled arteries extend toward the epithelium and anastamose to enhance the blood supply of the endometrium.
  • The menstrual phase of the cycle is initiated if fertilization does not occur. The corpus luteum fails because it is not rescued by the hCG from the placenta. The lack of progesterone results in vasoconstriction, ischemia, and the sloughing of tissue.

Placenta

If fertilization and implantation do occur, the menstrual phase of the uterine cycle is not initiated. Instead, the placenta develops at the site of implantation. This organ has several important functions. The placenta:

  • Facilitates the physiologic exchange between maternal and fetal circulations.
  • Serves as a selective filter for nutrients and maternal macromolecules like IgG.
  • Provides a site for gas exchange.
  • Serves as an endocrine organ secreting a number of hormones, which include hCG and progesterone.

The placenta is of both maternal and fetal origin. While its extremely complex development is beyond the scope of this course, it is important to understand for Cell Biology and Physiology. For Histology, you should understand the following:

  • There are two fetal cell types that contribute to the placenta, both of which are derived from the trophoblast. The cytotrophoblast layer contains mononuclear cuboidal cells that play a supportive role. The squamous syncytiotrophoblast layer is formed by fused cytotrophoblasts; it is therefore multinucleate and contains no internal cell membrane boundaries. This layer develops finger-like projections into the endometrium and secretes hCG, estrogen, and progesterone.
  • The syncytiotrophoblast layer forms the chorionic villi , which contain fetal blood vessels embedded in mesencyhmal tissue and extend into the lacunae of the endometrium, where they are bathed in maternal blood. This blood is found within the lacunae of the decidua basalis , which is derived from the stratum functionalis of the endometrium.
  • At first, there are five layers separating fetal and maternal blood: the syncytiotrophoblast layer, its basement membrane, cytotrophoblast cells, the endothelial cell basement membrane, and the endothelial cells lining the fetal capillaries. Over time, the cytotrophoblast layer regresses and the basement membrane of the syncytiotrophoblast may fuse with that of the fetal blood vessels. At this point there are merely three layers separating the maternal and fetal blood: the syncytiotrophoblast layer, the fused basement membrane, and the endothelial cells of the fetal capillaries.

Umbilical Cord

The umbilical cord connects the placenta to the developing fetus. It contains two umbilical arteries and one umbilical vein embedded in a connective tissue known as Wharton's jelly.

Pre-Lab Quiz

  1. How does the diffusion barrier between the mother and fetus compare with the air-blood barrier of the lung and the blood-urine barrier of the kidney?
  2. Answer:
  3. The external os of the cervix is the site of an important epithelial transition. Explain this transition and why it makes sense for each type of epithelium to exist in its respective region of the female reproductive tract.
  4. Answer:
  5. Name the stages of follicular development and the amount of genetic information contained in each.
  6. Answer:
  7. The chromosome number of oogonia and the secondary oocyte are both represented as "2N." Do these two stages possess identical DNA?
  8. Answer:

Slides

Please select whether to view the slides in study mode or quiz mode. In study mode, the images will contain labels and a description. In quiz mode, labels and description will be hidden.

  1. Ovary
  2. Primordial Follicles
  3. Early Primary Follicle
  4. Late Primary Follicle
  5. Secondary Follicle
  6. Graafian Follicle
  7. Corpus Luteum
  8. Lutein Cells
  9. Corpus Albicans
  10. Atretic Follicle
  11. Oviduct
  12. Oviduct Epithelium
  13. Uterus
  14. Cervix
  15. Vagina
  16. Uterine Cycle
  17. Placenta
  18. Chrorionic Villi
  19. Umbilical Cord

Virtual Microscope Slides

  1. Ovary
  2. Begin by distinguishing the medullary and cortical portions of the ovary.
  3. Corpus Luteum
  4. Observe the cells that comprise the corpus luteum at high magnification.
  5. Uterus
  6. Identify the stratum functionalis and the myometrium.
  7. Placenta
  8. At low magnification, identify the chorionic villi, select one, and increase the power to view it at high magnification.

Pathology

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  1. Pap Smear
  2. Cervical Intraepithelial Neoplasia

Quiz

  1. Name this stage of follicular development.
  2. Answer: Graafian follicle
  3. What is this structure?
  4. Answer: Atretic Follicle
  5. What 3 layers must a sperm cross to fertilize this?
  6. Answer: Corona radiata - Zona pellucida - Plasma membrane.
  7. What is the product of this structure?
  8. Answer: Progesterone and Estrogen
  9. Identify this structure.
  10. Answer: Primary Follicle
  11. Name the phase of the uterine cycle.
  12. Answer: Menstrual
  13. Name the phase of the uterine cycle.
  14. Answer: Secretory
  15. Name the phase of the uterine cycle.
  16. Answer: Proliferative
  17. Identify the normal Pap smear, and explain what is abnormal about the other smears.
  18. Answer: D is the normal Pap smear. A has a clearly dysplastic cell in the center, B shows a bacterial infection, and C is from a post-menopausal woman whose cells have undergone atrophy.
  19. Both the uterine and vaginal epithelium produce glycogen. What role does glycogen production play in each of these tissues??
  20. Answer: The uterine glycogen nourishes the egg as it develops in the endometrium. The vaginal glycogen is metabolized into lactic acid, which increases the acidity of the vagina to protect against bacteria.